Liver Function Testing and Sampling

5 major causes of hyperbilirubinemia

fasting, pre-hepatic, hepatic, post-hepatic and sepsis-associated

causes of FASTING hyperbilirubinemia

in horses, significant increases in bilirubin occur after fasting or anorexia → fasting leads to fat metabolism, which interferes with bilirubin uptake by hepatocytes and results in a usually mild hyperbilirubinemia

other findings associated with FASTING hyperbilirubinemia

liver enzymes and bile acids are normal, no signs of hemolytic anemia

most causes are mild with no jaundice, but in more severe cases jaundice is possible

causes of PRE-HEPATIC hyperbilirubinemia

acute hemolysis diseases (eg IMHA, leptospirosis in calves and lambs, theileriosis in cattle) → rate of bilirubin formation from RBC breakdown exceeds the capacity of hepatocytes to conjugate and excrete bilirubin (so it builds up in the blood)

findings associated with PRE-HEPATIC hyperbilirubinemia

liver enzymes and bile acids are usually normal, there is concurrent hemolytic (regenerative or pre-regenerative) anemia

causes of HEPATIC hyperbilirubinemia

acute or chronic liver disease (eg severe hepatitis due to various causes, FIP with significant liver involvement, liver failure) where there is extensive liver damage or decreased functional hepatic mass impairing bilirubin uptake and conjugation by the dysfunctional liver

findings associated with HEPATIC hyperbilirubinemia

often mild and not always significant to cause clinically detectable jaundice; leakage enzymes (ALT, etc) may be increased but are often normal; induction enzymes (ALP, etc) are usually normal but may be increased if there is concurrent cholestasis (eg cholangiohepatits)

causes of POST-HEPATIC (cholestatic) hyperbilirubinemia

cholestasis (usually due to obstruction) often causes regurgitation of bilirubin back into circulation

obstruction may be due to intrahepatic causes (eg hepatocyte swelling due to degeneration and necrosis, blocking bile canaliculi or duct) OR extrahepatic causes (eg neoplasia, inflammatory or other lesions which can compress, damage or block the bile ducts)

findings associated with POST-HEPATIC (cholestatic) hyperbilirubinemia

clinically detectable jaundice and increases in induction enzymes (ALP, GGT< etc) as well as bilirubinuria

if there is concurrent hepatocyte damage as well as cholestasis, ALT/GLDH will also be increased

causes of SEPSIS-associated hyperbilirubinemia

IN DOGS with severe bacterial infections; increases in inflammatory mediators (especially endotoxin) transport proteins available for bilirubin, resulting in decreased bilirubin excretion and retention in the blood

findings associated with SEPSIS-associated hyperbilirubinemia

inflammatory leukogram, toxic changes in neutrophils, hypoglycemia, marked hyperglobulinemia with FIP

animal is usually VERY clinically unwell

bile acids

normally synthesized and conjugated in the liver and excreted in the bile, ~95% are reabsorbed in the intestine and undergo recirculation into the portal blood back to the liver where they are removed from the blood and recycled back into bile again

there are only low levels of bile acids in the serum normally!

causes of increased serum bile acids

• decreased clearance of bile acids from the portal blood → due to moderate to severe reduction in functional liver mass or shunting of blood away from the liver (portosystemic shunt)

• decreased excretion of bile acids due to cholestasis (regurgitation of bile acids back into the peripheral blood)

ammonia

produced by the breakdown of dietary protein/amino acids by GIT bacteria and is removed from the portal circulation by the liver (where it is converted to urea)

causes of increased blood ammonia levels

markedly reduced hepatic mass or a portosystemic shunt due to decreased removal of ammonia from the portal blood

changes to albumin when hepatic function is impaired

liver cannot make enough albumin to maintain normal concentrations, resulting in hypoalbuminemia (only occurs with more chronic or chronic-active liver failure)

impact of hypoalbuminemia on calcium levels

body calcium is bound to albumin in the blood, so blood calcium is often concurrently low secondary to hypoalbuminemia in liver failure

clinical signs associated with very low albumin concentration

edema (ascites) due to the role albumin plays in maintaining colloid osmotic pressure that helps draw fluid into blood vessels

changes to urea value when there is liver disease

with significant impairment of liver function, the liver is unable to convert ammonia to urea as usual so blood ammonia levels increase, resulting in low blood urea levels

changes to cholesterol values when there is liver disease

impairment of hepatic function impairs cholesterol metabolism, resulting in decreased cholesterol synthesis (hypocholesterolemia)

changes to coagulation factors (APTT and PT) with liver disease

significant impairment of hepatic function can result in decreased production of coagulation factors and consequent defects in secondary hemostasis

• Increases in PT, APTT and ACT may be present on a coagulation panel in these cases

2 main options for liver sampling in a live animal

cytology (usually FNA) or histology (biopsy)

advantages of liver cytology:

quick, cheap, can generally be performed in the conscious patient

disadvantages of liver cytology:

less diagnostic than histology, gives no info about tissue architecture, easy to miss focal lesions (even with ultrasound guidance)

advantages of liver histology

looks at more tissue and tissue architecture, more likely to provided a diagnosis than cytology

disadvantages of liver histology:

time, cost, risk to patient (GA is usually required, hemorrhage is a risk)